Introduction An estimated 11.4% of South Africans are infected with HIV. As of 2007, 1.7 million people required antiretroviral therapy (ART) and only 460 000 were reported to be on ART. ART can improve the quality of life and socio-economic status for HIV positive patients. This study aimed at evaluating the role played by the different factors in influencing treatment adherence among HIV patients on ART. Methods The study was conducted on patients receiving out-patient ART in two district hospitals (one urban and the other rural) of Mpumalanga Province, South Africa. The study project was approved by the Research and Ethics Committee of the University of Pretoria as well as by the Mpumalanga Provincial Department of Health. This was an analytical, cross-sectional study. The sample size for the study was 490 (245 per site). Facility-based patient appointment registers for the period June-August 2008 were used as the sampling frame. The respondents were selected through systematic random sampling. An interviewer directed standardised questionnaire was administered to the respondents after securing voluntary informed consent. Data were also extracted from the attendance registers in the two facilities. Adherence was measured using the Patient Medication Treatment Adherence Questionnaire. The Pearson chi-square test of association and binary logistic regression analysis were used for identifying significant predictors of non-adherence variables. Results Four hundred and twenty nine questionnaires of the 488 returned questionnaires were analysed. Sixty one questionnaires were disqualified due to incompleteness of data. The response rate was 99.7% in both study areas and participants reported adherence was 92.54%. The median age of the respondents was 36 (IQR, 13), gender distribution was 21.13% males and 78.87% females. The median duration of treatment (in months) with ART was 15 months (IQR, 18). Treatment adherence was higher in the urban than in the rural hospital. The variables that were significantly associated with non-adherence were ‘urban residence’ (OR 0.39 [0.2-0.8]); ‘lack of social support’ (OR 2.74 [1.3-5.7]); Discussion There were also some qualitative variables that had a bearing on quality of healthcare services that could explain differences between the rural and urban sites. Social support and urban residence demonstrated association with treatment adherence. Copyright / Dissertation (MMed)--University of Pretoria, 2010. / School of Health Systems and Public Health (SHSPH) / Unrestricted

<b>Study 1:</b><div><b>Background:</b> Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. <b>Methods:</b> We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people living with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, “Difficulty falling or staying asleep?,” with the following response options: “I do not have this symptom” or “I have this symptom and…” “it doesn’t bother me,” “it bothers me a little,” “it bothers me,” “it bothers me a lot.” Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (<i>CI</i>). <b>Results:</b> For sCD14 and D-dimer, we observed no significant associations. For IL-6, veterans in the “bothers a lot” group had 15% higher IL-6 than veterans in the “I do not have this symptom” group in the demographic-adjusted model (exp[b]=1.15, 95%<i>CI</i>=1.02-1.29, <i>p</i>=.03). This association was nonsignificant in the fully-adjusted model (exp[b]=1.07, 95%<i>CI</i>=0.95-1.19, <i>p</i>=.25). <b>Conclusion:</b> We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.</div><div><p><b>Study 2:</b></p><p><b>Background:</b> While insomnia has been identified as a potential risk factor for cardiovascular disease in HIV (HIV-CVD), research on the underlying pathophysiological mechanisms is scarce. <b>Methods:</b> We examined associations between 0-to-12-week changes in sleep disturbance and the concurrent 0-to-12-week changes and the subsequent 12-to-24-week changes in markers of systemic inflammation, coagulation, and endothelial dysfunction among people living with HIV (<i>n</i> = 33-38) enrolled in a depression clinical trial. Sleep disturbance was measured using the Pittsburgh Sleep Quality Index. Inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) and coagulation marker D-dimer were determined from blood specimens; endothelial dysfunction marker brachial flow-mediated dilation (FMD) was determined by ultrasound. 0-to-12-week variables were calculated as 12-week visit minus baseline, and 12-to-24-week variables were calculated as 24-week minus 12-week. We constructed multivariate linear regression models for each outcome adjusting for age, sex, race/ethnicity, Framingham risk score, and baseline depressive symptoms. <b>Results:</b> We did not observe statistically significant associations between 0-to-12-week changes in sleep disturbance and 0-to-12-week or 12-to-24-week changes in IL-6, CRP, D-dimer, or FMD. However, we did observe potentially meaningful associations, likely undetected due to low power. For 0-to-12-weeks, every 1-standard deviation (<i>SD</i>) increase, or worsening, in the sleep disturbance change score was associated with a 0.41 pg/mL and 80 ng/mL decease in IL-6 and D-dimer, respectively. For 12-to-24-weeks, every 1-<i>SD</i> increase in sleep disturbance change score was associated with a 0.63 mg/L, 111 ng/mL, and 0.82% increase in CRP, D-dimer, and FMD, respectively. <b>Conclusion:</b> We observed potentially meaningful, though not statistically significant, associations between changes in sleep disturbance and changes in biological mechanisms underlying HIV-CVD over time. Some associations were in the expected direction, but others were not. Additional studies are needed that utilize larger samples and validated, comprehensive assessments of insomnia.</p></div>

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Introduction: In patients with HIV in antiretroviral treatment (ART) and virological failure to the first-line regimen, establishing a therapeutic regimen after having identified the M184V mutation, which confers ART resistance, represents a dilemma. Objective: To compare the virological response of the therapeutic regimens prescribed to patients with HIV who presented the M184V mutation in two national hospitals in Lima, Peru, during the years 2008 to 2019, and to determine the risk factors associated with poor virological response. Methods: A retrospective cohort study was developed based on the information of the HIV program participants with the M184V mutation. Results: A total of 175 participants were eligible for the study. The male sex predominated (75.4%), the current median age was 41 years [interquartile range (IQR) 35.84-47.47], and the time on ART was 89 months (IQR 57.7-124.53). The median initial viral load (VL) was 4.5 log10 copies/mL (IQR 3.97-5.09) and the time between genotyping and the change of therapy was 2 months (IQR 0-3.56). The most used antiretroviral regimen was protease inhibitor plus two nucleoside reverse transcriptase inhibitors (55.4%). With the protease inhibitor plus integrase inhibitor (PI + INI) ART, 69% less risk of poor virological response was obtained [p = .019 (confidence interval 95% 0.117-0.825)]. Conclusions: In patients with HIV and the M184V mutation, the PI + INI ART has shown a greater decrease in control VL and, thus, a good virological response. The risk factors associated with a poor virological response were the delay between genotyping and change of therapy, high levels of initial VL, and poor adherence among the participants. / Revisión por pares

Magister Chirurgiae Dentium (MChD) / MChD (Oral Pathology) minithesis, Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, University of Western Cape Among malignant lesions, lymphoma ranks second only to squamous cell carcinoma in frequency of occurrence in the head and neck. Lymphomas in HIV patients' are second in frequency to Kaposi's sarcoma as AIDS-defining tumours. About 50% of lymphomas in HIV patients are extranodal and more than half of these occur in the head and neck area. The number, variety and diagnostic complexity of lymphoma cases that have primarily arisen in the head and neck region has steadily increased in the surgical pathology service of the National Health Laboratory Services (NHLS) - Tygerberg. This observation is particularly relevant in the context of increasing HIV infection rates in the population of South Africa as demonstrated by a study in 2006 conducted by the Medical Research Council of South Africa. This is a retrospective study using the records of cases of head and neck lymphomas diagnosed at NHLS-Tygerberg over the last five years. The aim of this study is to investigate the prevalence of head and neck lymphomas (HNL) at NHLS-Tygerberg from January 2002 to December 2006. The objective of this study is to determine the frequency and types of HNL and to determine, if possible, an association between the incidence of HNL and the HIV status of the patients. Trends of prevalence in terms of gender, referral centres, HIV status, age of patients and site of presentation are also examined. The results of this study show an increase in the number of patients with HNL from January 2002 to December 2006. A significant increase is noted in the number of HIV positive patients documented each year, from 17% in 2002 to 33% in 2006. Western Cape- urban (WC-U) remains the largest referral center. A notable increase is seen, each year, in the number of patients referred to Tygerberg-NHLS from the Eastern Cape (EC) and Western Cape- rural (WC-R) areas. A significant number of HIV positive patients are referred from the Eastern Cape and Western Cape rural areas. The average age of disease presentation in the HIV positive group of patients is 35 years with the unknown group being 46 years and the HIV negative group being 54 years. The main categories of lymphoma that presented in HIV positive patients are plasmablastic lymphoma (PBL) and diffuse large B-celllymphoma (DLBCL), which together form 56% of cases. 26% of cases are Hodgkin's lymphoma (HL); the second largest group of HNL cases. Burkitt's lymphoma (BL) consists of 8% of cases. 7% of cases are T-cell lymphomas. 3% of cases are Mantle zone lymphomas. No cases of SLL and Follicular lymphomas (FL) are described in this group of patients. DLBCL and HL form 27% each of the cases in patients with a negative HIV status. A significant number of Follicular lymphomas (15%), small lymphocytic lymphoma (SLL) (9%), MALT (7%), and T-cell lymphomas (8%) are identified. No PBL are seen in this group of patients. The incidence of HNL at NHLS-Tygerberg has increased over the last five years. This trend parallels that seen in other developing countries such as Tanzania, Nigeria, Thailand and India. This increase is possibly due to an increase in the number of referrals to our center, an increase in the overall population of the Western Cape, an increase in the number of HIV positive patients and the high incidence of EBV infection in the general population of the Western Cape. Social issues, such as poverty, lack of adequate education, female dependence on partners, rural communities and the non-availability of anti-retroviral drugs (ARV) and highly active anti-retroviral therapy (HAART) to most of the population that require these drugs, are considered major contributing factors. A trend is noted in the increased number of female patients diagnosed each year with HNL. A predominance of DLBCL was identified in our series. This is consistent with previous reports and studies on HNL. The number of biologically aggressive lymphomas, such as DLBCL, Plasmablastic and Burkitt's lymphomas diagnosed each year, has also significantly increased. These were prevalent mainly in the HIV positive group of patients who were also younger compared to the HIV negative patients. The documented findings of this study will serve as a guideline for the estimation of head & neck lymphoma burden and risk assessment at NHLS- Tygerberg.

Thesis (MPH.) -- University of Limpopo, 2021 / Background: The provision and success of Antiretroviral therapy (ART) depend on monitoring and evaluation of treatment programmes which should be assessed during regular patient follow-ups. The treatment of HIV infection can only be effective if patients are retained in care and programme monitoring is adequately undertaken to understand the effectiveness of the emerging treatment. The outcome of patients lost to follow-up (LTFU) has received relatively little attention and it is predicted that these patients may have stopped taking antiretroviral drugs, resulting in high morbidity and mortality. The provision of ART was introduced into South African public health facilities in 2003 and therefore, attention has shifted from the immediate need to get patients into care, to the long-term challenges of keeping patients in care and on treatment. The objective of the current study was to determine the trends at which HIV-positive patients become LTFU on the ART programme at Shiluvana Local Area’s six clinics in the Greater Tzaneen Sub-District, Limpopo Province, South Africa. Methods: A retrospective cohort study approach was used and data was collected from the database of patients who were LTFU from 2012 – 2017 in the electronic data management system of the District Health Information System. Data was collected from 1161 patients. Data analysis was done using SPSS version 25, in which categorical data was presented using frequencies and percentages and comparisons between groups was done using Chi-square test for categorical data, and Student’s t-test for continuous data. A p-value of <0.05 was considered statistically significant. Univariate regression analysis was done to determine the contributory factors to LTFU for a period of more than 3 months. Results: The mean age of the study population was 36.5 years old ranging from 16 years to 87 years old and the age distribution of people who were LTFU for ART showed a significant association (p = 0.001). The study participants’ distribution by gender revealed that majority were females at 71.4%. The study findings also revealed there was a statistically significance difference in health status of the study population and majority of the LTFU were in the younger age group. The CD4 count of LTFU patients showed a statistically significance difference and majority of the LTFU in patients with a CD4 count of less than 200 were in younger age group also. The TB/HIV co-infection in the study population showed a statistically significance difference and majority of LTFU in the study did not have TB/HIV co-infection. The WHO clinical HIV staging in the study population did not show a statistically significance difference. Marital status, TB/HIV co-infection and WHO clinical staging were found to be a strong predictor of LTFU of more than 3 months. Conclusion: The study findings bring with them a number of recommendations such as there is a need to have a standardised tracking method of patients who migrate to other health facilities for their ART treatment. This will provide more accurate information regarding LTFU levels and reduce the misclassification of patients. The age group which is affected by LTFU in all variables was in the 20 – 34 years’ age group. This is of great concern, as this is the age group who are economically active and should contribute to the future economy of the country. It is therefore recommended that a greater focus should be placed in this age group, with policies and programmes that bring them into ART and retain them there. Lastly, educational campaigns, in a form of pamphlets and posters to emphasize adherence to ART and the importance of remaining on ART within designated health facilities. In conclusion, patients should be retained in care for as long as possible to prevent the prevalence of the ARV resistant virus that can impact negatively on the ART programme. Keywords: Antiretroviral treatment. Human immunodeficiency virus, Loss to follow-up, socio-demographic.

PURPOSE. Confocal laser scanning ophthalmoscopy (HRT; Heidelberg retinal tomograph II) and scanning laser polarimetry (GDx-variable corneal compensator [VCC]) were used to investigate whether early indicators of retinal nerve fiber layer (RNFL) thickness loss could be observed in patients infected with the human immunodeficiency virus (HIV) that had no associated retinopathy or optic neuropathy and were concomitantly receiving antiretroviral medications. METHODS. HRT and GDx-VCC parameters obtained from a group of 13 HIV-positive subjects (n = 26 eyes) on antiretroviral therapy examined with HRT, with a subgroup of six subjects (n = 12 eyes) examined with both HRT and GDx-VCC, were compared with those of a matched HIV-negative control cohort (13 subjects, n = 26 eyes) examined with HRT, with a subgroup of five subjects (n = 10 eyes) examined with both HRT and GDx-VCC. We employed generalized estimating equations for statistical analysis. RESULTS. Reduced mean values for the HRT height variation contour (p < 0.045) and HRT mean RNFL thickness (p < 0.023) were observed in HIV-positive subjects controlling for age, sex, and race. A significantly reduced mean value corresponding to the GDx-VCC superior maximum (p < 0.014) and inferior maximum (p < 0.016) were also observed for the HIV-positive cohort analyzed controlling for age, sex, and race. CONCLUSION. HRT and GDx-VCC indicators of RNFL thickness appear to be significantly reduced in HIV-positive subjects without retinopathy or optic nerve disease using antiretroviral medication, suggesting RNFL loss occurs in this population of HIV-positive patients. The lack of correlation between CD4 counts, viral load, number of antiretroviral medications used, or years from diagnosis of HIV and RNFL thinning, suggests that possibly other factors associated with HIV infection may contribute to the apparent RNFL thickness loss.

Student Number : 0106135V - MA research report - School of Human and Communitiy Development - Faculty of Humanities / The mass media persistently thrusts the awareness of risk of HIV/AIDS into our lives. The question is: how do people respond to this increased awareness and how do people cope with living in what has been termed ‘the risk society’? This can only be investigated within a given social and cultural context, in order to examine how individuals make sense of a perceived imminent crisis. This research has highlighted the prominent phenomenon of a widespread sense of personal invulnerability when faced with risk: the ‘not me’ dynamic in response to the negative Social Representations that surround this disease. Social representations Theory is a useful psychological framework as it approaches the study of perceptions of HIV risk by highlighting the emotional factors which are key to the human responses of risk while at the same time concentrating on the role of cognitive processing in the development of representations of social phenomena. The results from the HIV Knowledge, Perceptions & Practices questionnaire survey in this cross-sectional study with 200 Johannesburg university students indicate that while the large majority of the participants know a great deal about HIV, this knowledge is highly impacted upon by the Social Representations that exist around this virus. It is believed that the Social Representations surrounding HIV (death, pollution, the evil perpetrator etc.) can act as a barrier between intellectual knowledge of HIV and the related behaviour to reduce the risk of infection by distorting one’s perception of susceptibility of infection through the process of ‘othering’.

Thesis (MPH.) -- University of Limpopo, 2022 / Background: The Mother baby friendly initiative (MBFI) is an initiative that was launched in 1991 as a global programme to create an environment that enables and supports women to breastfeed their infants, providing advice to mothers and practical assistance to promote breastfeeding. This initiative plays an important role in improving infant’s nutritional status, growth, development and health for both mother and infant and supports exclusive breastfeeding. MBFI aims at increasing breastfeeding rate by supporting, protecting and promoting breastfeeding in health facilities. Aim: of the study is to explore the knowledge and challenges related to the implementation of the mother-baby friendly initiative at Standerton hospital. Method: A qualitative descriptive design was used to explore the knowledge and challenges related to the implementation of the mother-baby friendly initiative at selected hospital. Purposive sampling of the healthcare providers were the target population for the study as they are responsible for the implementation of MBFI in the hospital. In this research, data collected were in a form of interviews, audiotapes and written notes from interviews. Tesch’s eight steps in data analysis was used to analyse data. Results: The studies key theme and sub theme give the study’s findings and perspective of the issues found. The studies key theme were: 1. Knowledge of participants on MBFI at Standerton hospital, 2. Views about current practices of MBFI at Standerton –hospital and 3. Challenges regarding MBFI implementation at Standerton. MBFI was considered significant in the facility, however, due to inconsistences and challenges faced by the nurses the initiative was not fully implemented to improve breastfeeding rates. Conclusion: the study conclude that nurse’s had some knowledge on the MBFI initiative as they understood their role in breastfeeding advocacy and enhancing maternal and child health. There were significant challenges in MBFI implementation such as shortage of staff, lack of resources and training that hindered MBFI compliance and mothers not receiving the full benefits of the initiative, which contribute to decreased breastfeeding rates within the facility.

Background: Tuberculosis (TB) is a major global health threat that results not only in health consequences but also economic consequences. Since 2015 the World Health Organization (WHO) has developed a strategy with the aim of ending the global burden of TB by reducing TB-related deaths, reducing TB incidence, and eliminating the burden of TB-related catastrophic costs for patients and their families. In order to reach these targets, we need to implement effective TB diagnostic and care strategies that are feasible for both patients as well as the health care system. -- Methods: This study consists of two manuscripts which assess the economic burden of TB - one from the patient perspective and the other from the health system perspective. The first manuscript is a systematic review aimed to determine the costs incurred by patients and their households while receiving TB care with direct (medical and non-medical) as well as indirect costs being examined for the pre-diagnostic, post-diagnostic and total phase of care. It analyzed studies with varying patient populations from low-, middle-, and high-income settings to help estimate key factors that drive patient costs. Furthermore, it assessed the proportion of patients that incurred catastrophic costs and the coping strategies that they resorted to in order to offset the costs of TB care. The second manuscript is a modelling study which aimed to develop, parameterize and analyze a decision analytic model to determine the cost, health outcomes as measured by disability-adjusted life years (DALYs) averted and the cost-effectiveness of second-generation lateral flow lipoarabinomannan assay (SG LF-LAM) diagnostic algorithms in people living with HIV (PLHIV) per DALY averted. This model examined four different strategies - 1) the standard of care (SOC) Gene Xpert MTB/RIF only, 2) Gene Xpert MTB/RIF plus LF-LAM for all patients, 3) Gene Xpert MTB/RIF plus LF-LAM for patients with a negative Xpert result, and 4) Gene Xpert MTB/RIF plus LF-LAM for patients who are symptom negative. -- Results: A systematic review showed that total patient costs related to TB care ranged from a mean of $2.80 to $19,153.80 (2019 USD) with costs largely dependent on geographic location as well as patient population, Direct medical and indirect cost components were the largest source of costs for patients and their families while receiving TB care. Direct medical costs included the cost of medication, consultations, diagnostics, follow-up testing, and hospitalization while indirect costs mainly consisted of loss of income. The costs of TB care were considered catastrophic for the majority of patients resulting in them using coping strategies to offset the burden of costs. In the second manuscript, the cost-effectiveness analysis Xpert only was found to be dominated by Xpert + FujiLAM conditional on a negative Xpert with an ICER of 1,000 USD/per DALY averted compared to the standard of care (SOC) Xpert only. Sensitivity analysis found that variations in the key model parameters had an impact on the cost and effectiveness calculations obtained through the model. -- Conclusions: The burden of TB-related costs impact both patients and the health care system at all stages of TB care. Novel diagnostic strategies like the inclusion of FujiLAM for TB diagnosis in PLHIV are cost-effective tools that can aid in case detection and reduce severe outcomes of TB. In order to reduce the TB burden and achieve the "End TB" strategy goals, studies need to work to understand the key components involved in these costs as well as work to develop and implement effective, feasible interventions for TB diagnostics and care.

Despite our growing knowledge of virus biology they continue to present a problem to global public health. This problem arises from their high mutation rates that allow them to evade antiviral therapies that we have developed to date. An alternative solution for developing antiviral therapies could be to target host cell factors that are hijacked by the virus. The basis of this hypothesis is that if we can stop the virus from using host cell machinery or from evading host immune mechanisms we could treat the infection more efficiently. With the major research focus being on viral proteins and how we can prevent their functions, there is a lot of work to be done in finding host factors that could be the key to treating an infection. The three themes presented in this thesis broadly focus on this goal. The first theme looks at miRNAs, their interacting partners, and their dysregulation during HCV infection. A microRNA is identified from a small molecule screen of miRNAs that are dysregulated during HCV infection and its role in liver immunometabolism is examined to determine its antiviral potential and identify host factors that could be of interest to target with antiviral therapeutics. The second theme examines the potential of activity-based protein profiling techniques for complementing existing antiviral therapies. An azauracil probe is characterized to examine its ability to interact with viral polymerases and its suitability as a building block for antiviral research or therapies. The final theme uses activity-based protein profiling techniques to study a novel carbamate-hydrazone chemotype and establish its suitability as a chemical probe. The hydrazone probe’s reactivity with the mammalian proteome was determined and its interacting partners were identified using chemoproteomic techniques with an overall goal of examining its suitability for antiviral research. Overall, this thesis uses chemical and molecular biology techniques to present three differing perspectives on how to approach the discovery of host factors and develop novel antiviral therapies.